Many of these peer-reviewed journal articles below are available for free (open access). Please contact the lab for copies of materials that are not freely available.
Nam SA, Seo E, Kim JW, Kim HW, Kim HL, Kim K, Kim TM, Ju JH, Gomez IG, Uchimura K, Humphreys BD, Yang CW, Lee JY, Kim J, Cho DW, Freedman BS, Kim YK. Graft immaturity and safety concerns in transplanted human kidney organoids. Exp Mol Med. 2019 Nov 28;51(11):145. Analysis of the potential for kidney organoids to regenerate kidneys finds evidence of partial maturation, but also identifies critical areas for improvement.
Cruz NM and Freedman BS. Differentiation of human kidney organoids from pluripotent stem cells (2019). Methods Cell Biol. 153:133-150. Book chapter describing detailed protocol for our simple, standard method for growing and characterizing kidney organoids.
Kaverina NV, Eng DG, Moeller MH, Freedman BS, Miner JH, Pippin JW, Shankland SJ (2019). Dual lineage tracing shows that glomerular parietal epithelial cells can transdifferentiate towards the adult podocyte fate. Kidney Int. 96:3, 597–611. Tracking cells after injury provides clean insight into how podocytes – the kidney’s irreplaceable cells – get replaced.
Freedman BS and Ratner B. Building Scaffolds to Rebuild Kidneys (2019). ACS Cent. Sci. doi: 10.1021/acscentsci.9b00099. Perspectives on a new method to promote productive repair of injured kidneys, co-authored with bioengineering legend Dr. Buddy Ratner.
Freedman BS. Producing Purer Podocytes (2019). J. Am. Soc. Nephrol. 30(2):183-184. Dr. Freedman’s thoughts on a new protocol that generates podocytes from iPS cells at ~ 90 % purity.
Harder JL, Menon R, Otto EA, Zhou J, Eddy S, Wys NL, O’Connor C, Luo J, Nair V, Cebrian C, Spence JR, Bitzer M, Troyanskaya OG, Hodgin JB, Wiggins RC, Freedman BS, Kretzler M, European Renal cDNA Bank (ERCB), Nephrotic Syndrome Study Network (NEPTUNE). Organoid Single-Cell Profiling Identifies a Transcriptional Signature of Glomerular Disease (2019). JCI Insight 4(1):e122697. Use of single cell RNA sequencing in organoids reveals cell types, trajectories, and new information about how glomerular disease is a ‘reversal’ of kidney development. Open access!
Freedman BS. Better Being Single? Omics Improves Kidney Organoids (2018). Nephron, Dec 14;141(2):1-5. In-depth review by Dr. Freedman of a paper by Dr. Ben Humphrey’s lab comparing two organoid differentiation protocols using single cell RNA sequencing. Open access!
Czerniecki SM, Cruz NM, Harder JL, Menon R, Annis J, Otto EA, Gulieva RE, Islas LV, Kim YK, Tran LM, Martins TJ, Pippin JW, Fu H, Kretzler M, Shankland SJ, Himmelfarb J, Moon RT, Paragas N, Freedman BS. High-throughput screening enhances kidney organoid differentiation from human pluripotent stem cells and enables automated multidimensional phenotyping. Cell Stem Cell, doi: 10.1016/j.stem.2018.04.022. The use of automated robots to produce organoids takes kidney differentiation and phenotyping to the next level.
Cruz NM, Freedman BS† (2018). CRISPR gene editing in the kidney. Am. J. Kidney Dis. 71(6):874-883. A review of how CRISPR is revolutionizing nephrology research and clinical practice.
Hamatani H, Eng DG, Kaverina NV, Gross KW, Freedman BS, Pippin JW, Shankland SJ. Lineage tracing aged mouse kidneys show lower number of cells of renin lineage and reduce responsiveness to RAAS inhibition (2018). Am. J. Phys. – Renal Phys., doi: 10.1152/ajprenal.00570.2017. Studies of specialized ‘podocyte replacement’ cells reveals how aging affects kidney regeneration.
Jing P, Liu Y, Keeler EG, Cruz NM, Freedman BS, Lin LY (2018). Optical tweezers system for live stem cell organization at the single-cell level. Biomed. Optics Express 9:2, 772-779. Development of a new biophysical tool to manipulate and study stem cells.
Eng DG, Kaverina NV, Schneider RRS, Freedman BS, Gross KW, Miner JH, Pippin JW, Shankland SJ (2018). Detection of transdifferentiation in the kidney glomerulus with dual lineage tracing. Kidney International 93:1240-1246. A two-color labeling system provides strong evidence that renin lineage cells can transdifferentiate after injury to replace podocytes.
Cruz NM, Song X, Czerniecki SM, Gulieva RE, Churchill AJ, Kim YK, Winston K, Diaz M, Fu H, Finn LS, Pei Y, Himmelfarb J, Freedman BS (2017). Organoid cystogenesis reveals a critical role of microenvironment in human polycystic kidney disease. Nature Materials, 16:1112–1119. In permissive microenvironments, kidney organoids with PKD mutations swell up to sizes easily seen by the naked eye.
Kim YK, Refaeli I, Brooks CR, Jing P, Gulieva RE, Hughes MR, Cruz NM, Liu Y, Churchill AJ, Wang Y, Fu H, Pippin JW, Lin LY, Shankland SJ, Vogl AW, McNagny KM, Freedman BS (2017). Gene-edited human kidney organoids reveal mechanisms of disease in podocyte development. Stem Cells, 35:12, 2366-2378. CRISPR’d organoids reveal how the podocyte gets its legs.
Shankland SJ, Freedman BS, Pippin JW (2017). Can podocytes be regenerated in adults? Curr Opin Nephrol Hypertens. 26(3):154-164. In this review paper, we discuss the ability of podocytes, the kidney’s filtering cells, to regenerate naturally, and the ramifications of these findings for clinical nephrology.
Tögel F, Valerius MT, Freedman BS, Iatrino R, Grinstein M, Bonventre JV (2017). Repair after nephron ablation reveals limitations of neonatal neonephrogenesis. JCI Insight 2(2):e88848. In this study, we show that mammalian kidneys cannot regenerate new nephrons, even when injury occurs only shortly after birth.
Pang P, Abbott M, Chang SL, Abdi M, Chauhan N, Mistri M, Ghofrani J, Fucci QA, Walker C, Leonardi C, Grady S, Halim A, Hoffman R, Lu T, Cao H, Tullius SG, Malek S, Kumar S, Steele G, Kibel A, Freedman BS, Waikar SS, Siedlecki AM (2017). Human vascular progenitor cells derived from renal arteries are endothelial-like and assist in the repair of injured renal capillary networks. Kidney Int. 91(1): 129-143. A study by our collaborator Dr. Siedlecki identifying a new population of adult stem cells for repairing blood vessels.
Freedman BS, Zeidel ML, Steinman TI (2016). Technology and the future of kidney care. Nephrol. News Issues 30(11): 24-28 (review). A look at kidney medicine 30 years in the future.
Freedman BS (2015). Modeling kidney disease with iPS Cells. Biomarker Insights 2015:Suppl. 1 153-169 doi: 10.4137/BMI.S20054. A summary of recent progress in the field, including differentiation of kidney organoids and the use of genome editing techniques such as CRISPR.
Freedman BS, Brooks CR, Lam AQ, Fu H, Morizane R, Agrawal V, et al. (2015). Modelling kidney disease with CRISPR-mutant kidney organoids derived from human pluripotent epiblast spheroids. Nat. Commun. 6:8715 doi: 10.1038/ncomms9715. This study describes a new, simple protocol for generating human mini-kidney organoids from stem cells, and uses gene-edited kidney organoids to re-create human kidney disease in a petri dish.
Morizane R, Lam AQ, Freedman BS, Kishi S, Valerius TM, Bonventre JV (2015). Nephron organoids derived from human pluripotent stem cells model kidney development and injury. Nat. Biotech doi:10.1038/nbt.3392. A new protocol for differentiating ES and iPS cells into kidney organoids that resemble kidney tissue.
Freedman BS, Steinman TI (2015). Stem cells represent a new area of kidney care. Nephrol. News Issues 29(8): 18-20 (review). An analysis of the potential for iPS cells in kidney clinical research and medicine.
Lam AQ, Freedman BS, Bonventre JV (2014). Directed differentiation of pluripotent stem cells to kidney cells. Semin Nephrol 34(4): 445-461 (review). A summary of recent progress and remaining challenges in using human pluripotent stem cells for kidney regeneration and disease modeling.
Lam AQ*, Freedman BS*, Morizane R*, Valerius MT, Bonventre JV (2014). Rapid and efficient differentiation of human pluripotent stem cells into intermediate mesoderm which forms tubules expressing kidney proximal tubular markers. J Am Soc Nephrol 25(6): 1211-1225. This paper introduces a new protocol for rapidly converting ES and iPS cells into mesoderm and subsequently kidney progenitor cells.
Freedman BS,* Lam AQ,* Sundsbak JL, Iatrino R, Su X, Koon SJ, Wu M, Daheron L, Harris PC, Zhou J, Bonventre JV (2013). Reduced ciliary polycystin-2 in iPS cells from PKD patients with PKD1 mutations. J Am Soc Nephrol 24: 1571-1586. In this paper, we generated iPS cells from patients with autosomal dominant and recessive PKD, and used them to identify a possible therapeutic approach.
Xiao B,* Freedman BS,* Miller KE, Heald R, and Marko JF (2012). Histone H1 compacts DNA under force and during chromatin assembly. Mol Biol Cell 23(24):4864-71. This paper measures that histone H1 compacts individual molecules of DNA under force, protecting them from shear stress during complex nuclear remodeling processes.
Fu H, Freedman BS, Lim CT, Heald R, and J Yan (2011). Atomic force microscope imaging of chromatin assembled in Xenopus laevis egg extract. Chromosoma 120(3):245-54. This paper introduces a novel method to examine chromatin structure under physiological conditions, in contrast to the highly purified and simplified conditions typically used in the lab.
Freedman BS, Miller KE, and R Heald (2010). Xenopus egg extracts increase dynamics of histone H1 on sperm chromatin. PLoS ONE 5(9): e13111. This paper shows that histone H1 rapidly binds and releases chromatin in physiological cytoplasm, but gets stuck on chromatin in non-physiological buffer. This paper is freely available.
Freedman BS and R Heald (2010). Functional comparison of H1 histones in Xenopus reveals isoform-specific regulation by Cdk1 and RanGTP. Current Biology 20(11):1048-1052. This paper shows that negative charges and cyclin-dependent phosphorylation of histone H1 at mitosis actually enhance its binding to chromosomes, contrary to the existing dogma in the field.
Maresca TJ, Freedman BS, and R Heald (2005). Histone H1 is essential for mitotic chromosome architecture and segregation in Xenopus laevis egg extracts. J. Cell Biol. 169(6):859-869. This paper shows that mitotic chromosomes assembled without histone H1 are long and “stringy,” causing problems during cell division. This paper is freely available.
* = co-first authors
